Disease relevance of Snai2

• Relevance of this model was suggested by verification that three of these genes (IGFBP5, HSIX1, and Slug) were also expressed in alveolar rhabdomyosarcoma cell lines [1].
• CONCLUSIONS: Slug expression can predict the clinical outcome of lung adenocarcinoma patients [2].
• RESULTS: High expression of Slug mRNA in lung cancer tissue was significantly associated with postoperative relapse (P = 0.03) and shorter patient survival (P < 0.001) [2].
• OBJECTIVES: The transcriptional factors Snail and Slug have been reported to be important in cell migration during development and also during tumor metastasis [3].
• Snail and Slug are major determinants of ovarian cancer invasiveness at the transcription level [3].

High impact information on Snai2

• Thus, Slug functions downstream of p53 in developing blood cells as a critical switch that prevents their apoptosis by antagonizing the trans-activation of puma by p53 [4].
• Analysis of microarray data from human nevi shows that the expression pattern of Slug, a master regulator of neural crest cell specification and migration, correlates with those of other genes that are important for neural crest cell migrations during development [5].
• Moreover, Slug is required for the metastasis of the transformed melanoma cells [5].
• We tested for a central role in EMT of a zinc-finger protein called Slug [6].
• The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition [6].

Biological context of Snai2

• Slug (approved gene symbol Snai2), a member of the Snail gene family of zinc-finger transcription factors, is believed to function in the maintenance of the nonepithelial phenotype [7].
• The identification of Slugh, a zinc-finger transcription factor expressed in migratory neural crest cells, as the gene responsible for pigmentary disturbances in mice prompted us to analyse the role of its human homologue SLUG in neural crest defects [8].
• Reporter analysis revealed Snail and Slug suppressed the promoter activity of Col2a1, and the E-boxes in the promoter region were the responsible element [9].
• To investigate the potential role of SLUG overexpression in development and in cancer, we generated mice carrying a tetracycline-repressible Slug transgene [10].
• We have characterized Slugh gene expression during early mouse embryogenesis by whole mount in situ hybridization of Slugh mRNA and through detection of beta-galactosidase expression from an in-frame SlughIacZ allele generated through homologous recombination [11].

Anatomical context of Snai2

• We uncovered new details regarding Snai1 function during gastrulation and left-right asymmetry determination, while surprisingly showing that neither the Snai1 nor Snai2 genes are essential for neural crest cell delamination [12].
• Zinc-finger transcription factor Slug contributes to the function of the stem cell factor c-kit signaling pathway [13].
• In situ hybridization analysis of developing mouse limb demonstrated that Snail and Slug mRNAs were highly expressed in hypertrophic chondrocytes [9].
• Slug, a member of the snail/slug family of zinc finger transcriptional repressors critical for mesoderm/ectoderm development, was further shown to be a downstream target by using promoter/reporter constructs and demonstration of defective muscle regeneration in Slug null mice [14].
• Slugh expression is first detected in extraembryonic mesoderm and is later detected in many mesodermal subsets, although it is not detected in the primitive streak [11].

Physical interactions of Snai2

• Detailed analysis of the binding affinity of different repressors to the E-pal element indicates that Slug binds with lower affinity than Snail and E47 proteins [15].

Regulatory relationships of Snai2

• However, the overexpression of Slug was not able to upregulate Sox10 expression [16].

Other interactions of Snai2

• Two members of this family have been described in higher vertebrates, Snail (Sna) and Slug (Slu), where they have been implicated in the formation of tissues such as the mesoderm and the neural crest [17].
• The radioresistance biological function of the SCF/kit signaling pathway is mediated by the zinc-finger transcription factor Slug [18].
• This effect of Sox10 depletion is produced during some of the earliest steps of neural crest specification, as is shown by the inhibition in the expression of Slug and FoxD3, which are early markers of neural crest specification [16].
• Stable expression of Slug in MDCK cells leads to the full repression of E-cadherin at transcriptional level and triggers a complete epithelial to mesenchymal transition [15].

Analytical, diagnostic and therapeutic context of Snai2

• We established the physiologic significance of Slug-mediated repression of puma by demonstrating that mice deficient in both genes survive doses of total-body irradiation that lethally deplete hematopoietic progenitor populations in mice lacking only slug [4].
• Our results indicate that Slug induces the first phase of growth factor-induced EMT, including desmosome dissociation, cell spreading, and initiation of cell separation [6].
• The overexpression of Slug enhanced xenograft tumor growth and increased microvessel counts in angiogenesis assay [2].
• A total of 15 novel Slug target species were validated by real-time PCR or Western analyses [7].
• Mouse cDNA microarray analysis uncovers Slug targets in mouse embryonic fibroblasts [7].

References